Non-invasive brain stimulation to stimulate neuroplasticity, enhance recovery, and improve mood after stroke has made substantial technical advances in the past two decades. The most common neuromodulatory techniques are transcranial direct current stimulation (tDCS), applying a weak electrical current across the brain, and transcranial magnetic stimulation (TMS), inducing an electrical field within the brain. Currently, the only non-invasive brain stimulation technique and indication for which there is a sufficiently strong evidence base to support routine use in clinical practice is transcranial magnetic stimulation to improve mood in post-stroke depression. TMS applied to dorsolateral prefrontal cortices can substantially reduce depressive symptoms, though not increase complete remission. TMS is a reasonable second-line intervention in patients with post-stroke depressed mood who have been resistant to pharmacotherapy. For several additional indications in post-stroke patients, both TMS and tDCS have shown signals of potential benefit in randomized trials. The strongest evidence is for enhancement of recovery of upper extremity motor function and hand dexterity with TMS. In addition, there is suggestive evidence for possible benefit in improving recovery of function after stroke in walking (TMS), activities of daily living (tDCS), aphasia (both), hemispatial neglect (both), and swallowing (both). However, for these and potentially other recovery-enhancing applications, substantial additional larger trials are needed.

Pre-clinical studies provide clear and consistent evidence that a variety of centrally acting drugs affecting specific neurotransmitters can either facilitate or interfere with functional recovery after brain injury. Although at least some clinical trials suggest similar effects in humans, results have been inconsistent. The impact of important factors such as drug dose, duration, and intensity of physiotherapy, and timing between injury and treatment are difficult to translate from preclinical studies. Issues related to variability in stroke severity, location of injury, and comorbid conditions further complicate trial design and could obscure a true treatment effect. Because of these and other issues, the design of efficacy trials assessing putative neuro-restorative interventions is not trivial. Although a proven pharmacological approach resulting in a clinically meaningful improvement in post-stroke recovery remains elusive, it is reasonable to avoid medications that may have harmful effects in patients who have had a stroke. It is also important to control for these possible harmful effects in future clinical trials assessing the outcomes of stroke patients after the acute period.